Effectiveness of oral antiviral agents on long‐term cardiovascular risk in nonhospitalized patients with COVID‐19: A multicenter matched cohort study

Abstract

AbstractAlthough a novel oral antiviral agent can improve short‐term COVID‐19 outcomes, its effects on the long‐term outcomes, namely the risk of major adverse cardiovascular events (MACEs), remains unknown. This retrospective cohort study used the TriNetX research network to identify nonhospitalized adult patients with COVID‐19 between March 1, 2020, and January 1, 2022. A propensity score matching method was used to form two matched cohorts with and without receiving nirmatrelvir–ritonavir (NMV‐r) or molnupiravir. The primary outcome was the incidence of MACEs within a 30‐day to 1‐year period following a diagnosis of COVID‐19. Two cohorts of each 80 888 patients with balanced baseline characteristics were formed using propensity score matching. During the follow‐up period, 976 patients in the study group and 1609 patients in the control group developed MACE. Overall, the study group had a significantly lower risk of MACE than the control group (hazard ratio [HR], 0.683; 95% confidence interval: 0.630–0.739). The significantly lower HRs of overall MACEs were consistently observed in most subgroup analyses (age: >41–≤64 years: 0.60 [0.52–0.89]; age: ≥65 years: 0.68 [0.62–0.76]; women: 0.63 [0.57–0.71]; men: 0.62 [0.55–0.70]; vaccinated: 0.74 [0.63–0.88]; unvaccinated: 0.66 [0.60–0.73]; NMV‐r; 0.65 [0.59–0.71]; and molnupiravir: 0.75 [0.61–0.92]). In conclusion, novel oral antiviral agents, namely NMV‐r and molnupiravir, were effective in reducing long‐term MACEs among nonhospitalized patients with COVID‐19, particularly when treated with NMV‐r or in patients aged ≥40 years. These findings suggest the potential role of novel antiviral agents as a preventive measure to reduce further adverse cardiovascular outcomes.